Timothy E. Bunchman, MD
Megan M. Lo, MD
BASICS
DESCRIPTION
• National Kidney Foundation (NKF) defines chronic kidney disease (CKD) as evidence of structural or functional kidney abnormalities (abnormal urinalysis, imaging studies, or histology) that persist for at least 3 mo, with or without a decreased glomerular filtration rate (GFR), as defined by a GFR of <60 mL/min per 1.73 m2 (1)
– This definition is not applicable to children younger than 2 yr, because they normally have a low GFR, even when corrected for body surface area
• CKD in pediatrics
– 70% tubular interstitial disease (TID)
– 30% chronic glomerular disease (CGD).
• CKD in children is often related to congenital abnormalities. The presentation often can be silent or associated with: Polyuria and polydipsia and failure to grow.
• TID is often congenital and associated with different syndromes: Posterior urethral valves (PUVs), Eagle-Barrett syndrome (EBS), and renal dysplasia (most genetic syndromes are associated with dysplasia).
• CGD is often associated with hypertension, hematuria, proteinuria, and edema.
• The peak age of the diagnoses of end-stage renal disease is about 5 yr of age. The second age of presentation of loss of kidney function is around the age of puberty.
EPIDEMIOLOGY
Incidence
10–15 cases per million per year
Prevalence
50–100 per million per year
RISK FACTORS
• Primary risk factor for dysplasia is associated congenital diseases and/or syndromes.
• Familial renal disease; may present at any age
– Alport syndrome
– Benign familial hematuria
– IgA nephropathy
– Polycystic kidney disease
• Higher in males, African Americans
Genetics
Diverse based upon cause. For example, mutations in HNF1B are causative for cystic dysplasia of the kidney.
PATHOPHYSIOLOGY
• In interstitial renal disease, the degree of CKD is related to the amount of renal mass. In those patients who were born with small kidneys or have associated obstructive uropathy (PUV, EBS, megaureter syndrome) often will have early progressive loss of renal function.
• Glomerular-based renal disease is more common in the school age and greater population.
– The clinical presentation of glomerulonephritis is associated with edema, hypertension, as well as blood and protein in the urine; most need a renal biopsy.
ASSOCIATED CONDITIONS
• Hearing loss
• Short stature
GENERAL PREVENTION
• In CKD associated with congenital renal disease there is no true prevention.
• Often the use of prenatal ultrasounds can identify infants at risk but they are not 100% diagnostic.
– Serial ultrasounds over time may identify lack of interstitial renal disease, primarily looking for renal growth.
– Further, a low level of amniotic fluid at the time of birth also correlates with poor renal function.
• Prevention from a glomerular-based renal disease is limited as these are usually related to autoimmune diseases. Therefore, the general prevention in all areas of CKD is prevention of complications of CKD.
DIAGNOSIS
• In glomerular-based renal disease the history is associated with grossly bloody urine, hematuria, proteinuria, hypertension, and edema. Tissue pathology is generally needed for diagnosis.
• In the review of systems, the findings of polyuria, polydipsia, and exclusion of diabetes is important. These children also can have associated growth impairment.
• Family history is important in certain renal disease, specifically in the area of the familial renal disease such as IgA nephropathy, Alport, polycystic kidney disease, and rarely benign familial hematuria.
– In addition, eliciting a history of reflux nephropathy, recurrent urinary tract infections, and congenital renal abnormalities within the family is important.
– Further a family history of dialysis or transplantation or unexplained hypertension earlier in life may be important.
• In the classic Alport syndrome (a male predominant disease) there is an association with high-frequency hearing loss, often in the 2nd or 3rd decade of life.
PHYSICAL EXAM
• Often these children have a benign exam
– In TID, the blood pressure and poor growth are important.
– In CGD, kids often have hypertension.
– Can have associated edema, ascites, and cardiovascular abnormalities.
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Basic metabolic panel, renal function testing
• Regardless of the etiology of CKD, at levels of CKD 3 or greater (roughly 50% kidney function), one can have:
– Metabolic acidosis (low CO2)
– Abnormal parathyroid activity
Low calcium, elevated phosphorus, and elevated PTH
– Anemia that is usually related to a combination of iron deficiency, as well as the lack of natural erythropoiesis.
• C3 C4 complement
– Decreased in some glomerulonephritis and lupus nephritis
• Urinalysis:
– In TID, the urine is usually benign with inability to concentrate the urine regardless of the time of day.
– In CGD, often these patients can have blood and protein and red cell casts.
• Urine protein: Creatinine ratio, rarely 24-hr urine for protein.
Imaging
• In TID the renal imaging is important.
– Often these patients can have normal to small looking kidneys seen on ultrasound. The echogenic texture will be important. Further, some degree of obstructive uropathy may be seen.
– Voiding cystourethrogram may be indicated
– In those patients who have obstructive uropathy, either at a UPJ or UVJ, a diuretic renal scan or MAG3 scan may be important.
• In CGD, renal imaging may show nephromegaly. Otherwise, ultrasound will be nonspecific.
Diagnostic Procedures/Surgery
• In glomerular-based renal diseases renal biopsy is often required.
• Indication for biopsy in patients with CGD is: A normal complementemic glomerulonephritis or a persistent low C3, and a low C4.
• Other indications: Glomerulonephritis associated with an elevated anti-dsDNA (lupus), hemoptysis with associated renal glomerulonephritis (pulmonary, renal disease), and in patients with persistent low C3 without normalization after 12 wk, which excludes postinfectious glomerulonephritis (historically poststreptococcal glomerulonephritis).
Pathologic Findings
• Histologic analysis in interstitial renal disease is not essential.
• In glomerular-based renal diseases, renal biopsy is often required.
• Depending on underlying cause, the pathologic findings are vastly different on H&E, immunofluorescence, and electron microscopy.
DIFFERENTIAL DIAGNOSIS
• As mentioned for TID, polyuria, polydipsia can also be associated with diabetes, which is an easy diagnosis to exclude based on urinalysis and blood work.
• Differential diagnosis of CKD is limited to underlying disease
– Congenital renal anomalies: Obstructive uropathy, renal hypoplasia or dysplasia, reflux nephropathy, polycystic kidney disease
– Glomerular disease: Focal segmental glomerulosclerosis (FSGS).
– Others: Hemolytic uremic syndrome, genetic diseases (cystinosis, oxalosis, Alport syndrome), interstitial nephritis
– Rare in childhood: Diabetic nephropathy and hypertension
TREATMENT
GENERAL MEASURES
• In chronic interstitial renal disease with polyuria/polydipsia, more fluid and sodium are needed to maintain euvolemia.
• In both groups, attention to potassium and phosphorus load is important.
• All NSAIDS should be avoided. Levels of potential nephrotoxins, if measurable such as vancomycin or gentamicin, should be followed at least twice weekly; with an initial level no later than 24–48 hr after starting.
• Damage from CT contrast should be minimized with pre- and postprocedure IV hydration.
MEDICATION
First Line
• Treatment of metabolic acidosis with either liquid form of Bicitra or the pill form of bicarbonate to normalize the CO2. This will preserve growth as well as bone integrity.
• Treatment of phosphorus restriction, phosphorus binding (nonaluminum binders such as CaCO3, Calcium acetate, or sevelamer products), and institution of vitamin D to preserve and prevent secondary hyperparathyroidism and prevent bone disease.
• Treatment with replacement doses of iron sucrose 1–3 mg/kg per dose and use of erythropoietic agents (epoetin, darbepoetin) are used for anemia.
Second Line
• Those that were mentioned above including antihypertensive agents if indicated.
• Often ACE inhibitors and angiotensin receptor blockers (ARBS) are used for glomerular-based renal disease because of proteinuria but are contraindicated in possible pregnancy (birth defects) and low GFR (renal failure, hyperkalemia)
SURGERY/OTHER PROCEDURES
In TID, patients may require cystoscopy with ablation of PUVs. UPJ or UVJ obstructions may need to be relieved. Reflux may need to be corrected, if high grade and not resolving spontaneously.
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
Dialysis (peritoneal or hemodialysis) or kidney transplant should be considered when GFR falls into the 20’s or growth and metabolic control can no longer be maintained with medical management.
Complementary & Alternative Therapies
• Nutrition is important: At least 2 g/kg/d protein would be needed in order to maintain adequate protein stores and growth.
• Nutrition in CGD is associated with salt and water restriction. Therefore, the nutrition construction may be opposite in terms of the sodium and water load.
ONGOING CARE
PROGNOSIS
• Difficult to predict early in life.
• Lack of renal growth with a creatinine greater than 1 at a year of age, associated hematuria, proteinuria, and hypertension in patients with TID portends the need for future dialysis and transplantation.
• CGD prognosis is directly related to underlying cause.
• Certain diseases such as lupus, Wegener, Goodpasture, membranous nephropathy, and IgA nephropathy can be amenable to therapy.
• Other renal diseases such as focal sclerosis maybe less amenable to therapy.
COMPLICATIONS
• Growth impairment in children is a known complication, independent of the etiology of CKD (2)
• Hypertension is also a risk factor.
• Protein restriction, used in adult CKD to slow disease progression, cannot be used with kids as this would further hinder their growth and development.
FOLLOW-UP
• Newborns and infants should be seen as frequently as every 1–2 wk in order to ensure maintenance of euvolemia.
• Primary care physicians need to be instructed that patients with interstitial disease will get dehydrated more quickly than the average patient; therefore, attention to their care at the time of vomiting and diarrhea is important for these patients will become volume depleted in a hurry.
Patient Monitoring
Glomerular-based renal diseases are associated with salt and water restriction as well as blood pressure control.
Patient Resources
• American Society of Pediatric Nephrology. www.aspneph.com/parentpatient.asp
• National Kidney Disease Educational Program. www.nkdep.nih.gov
• NKF Cares: Patient Information Center. www.kidney.org/patients
REFERENCES
1. National Kidney Foundation. K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis. 2002;39:S1–S266.
2. Wesseling-Perry K. Bone disease in pediatric chronic kidney disease. Pediatr Nephrol. 2013;28:569–576.
ADDITIONAL READING
• Avner ED, Harmon WE, Niaudet P, et al., eds., Pediatric Nephrology. 6th ed. Springer; 2009.
• Geary DF, Schaefer F, eds. Comprehensive Pediatric Nephrology. 1st ed. Mosby; 2008.
See Also (Topic, Algorithm, Media)
• Acute Kidney Injury, Pediatric (Renal Failure, Acute)
• Megaureter, Congenital
• Posterior Urethral Valves
• Prune Belly (Eagle-Barrett or Triad) Syndrome
CODES
ICD9
• 582.89 Chronic glomerulonephritis with other specified pathological lesion in kidney
• 585.9 Chronic kidney disease, unspecified
• 753.8 Other specified anomalies of bladder and urethra
ICD10
• N03.9 Chronic nephritic syndrome with unsp morphologic changes
• N18.9 Chronic kidney disease, unspecified
• Q64.79 Other congenital malformations of bladder and urethra
CLINICAL/SURGICAL PEARLS
• Patients with interstitial disease or obstructive uropathy require IV hydration while NPO prior to procedures.
• In contrast to adults, diabetic nephropathy and hypertension are rare causes of CKD in children.
• Small changes in creatinine reflect large changes in GFR for children with CKD.
• Baseline creatinine with attention to any changes after potential renal insult (CT contrast, hypovolemia/hypertension, medications, etc.) is an important measure for monitoring and prevention of progression of CKD.